There are two main types of diabetes. Type 1 diabetes (or “juvenile diabetes”) is caused by an absolute insulin deficiency as a result of damaged B cells or B cell death that is frequently associated with insulitis. Type 2 diabetes (or “adult onset diabetes”) is principally caused by an insulin resistance of the tissue. This insulin resistance is accompanied by relative insulin deficiency and increased glucose production in the liver. In many cases, type 2 diabetes is also accompanied by insulitis. Cellular damage or inflammation of the islets of Langerhans of the pancreas can impair the functioning of the insulin-producing B cells or lead to a complete loss of function due to B cell death. This results in an absolute insulin deficiency, which causes insulin-depending diabetes mellitus (IDDM). IDDM mainly occurs in children, youths or adolescents. However, it can also demonstrate onset in advanced age. In this case, it is called “latent autoimmune diabetes of the adult” (LADA).
The most important aspect of inflammation of the islets of Langerhans is an infiltration by macrophages and T-lymphocytes. During the activation of the TH1-lymphocytes, B cells can be destroyed due to apoptosis resulting in the progression of the disease. The apoptosis does not affect the A cells or D cells (the glucagon of the A cells increases the blood glucose level, and the somatostatin of the D cells inhibits the secretion of insulin).
Without insulin substitution, this condition eventually leads to death due to diabetic coma. Previous attempts to suppress the course of the diabetic disease, e.g. by administering anti-inflammatory agents such as non-steroidal antiphlogistic agents, glucocorticoids (the latter even having a diabetogenous effect), immunosuppressants, or by immune intervention and immune prevention, e. g. by administering cyclosporine A, have not led to a satisfactory solution. In fact, these therapeutic attempts have rather considerable side effects. Other therapeutic approaches such as the treatment with methotrexate, nicotinamide, monoclonal antibodies, azothioprine etc. have not proven to be suited either to influence damage of B-cells in a way that is efficient for the diabetic person with little side effects. Neither has the use of anti-inflammatory agents that act selectively such as COX2-inhibitors (US 2003/0017148) led to success.